A5076553395- Lymphoma Diagnosis and Treatment
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Mast cells and histamine
- Cancer, Hypoxia, and Metabolism
- Pancreatic and Hepatic Oncology Research
- Glycosylation and Glycoproteins Research
- Advanced Proteomics Techniques and Applications
- Cancer-related gene regulation
- Immunotherapy and Immune Responses
- Pancreatitis Pathology and Treatment
- Chronic Lymphocytic Leukemia Research
- Viral-associated cancers and disorders
- Genetic Neurodegenerative Diseases
- Genetics and Neurodevelopmental Disorders
- Cancer, Lipids, and Metabolism
- Selenium in Biological Systems
- Chronic Myeloid Leukemia Treatments
- RNA Research and Splicing
- ATP Synthase and ATPases Research
- Monoclonal and Polyclonal Antibodies Research
- Mitochondrial Function and Pathology
- Clostridium difficile and Clostridium perfringens research
- Birth, Development, and Health
- Carbohydrate Chemistry and Synthesis
University of Michigan
2015-2025
Ann Arbor Center for Independent Living
2025
University College Dublin
2025
Trinity College Dublin
2008-2024
Tallaght University Hospital
2008-2024
St. Vincent's University Hospital
2019
Abstract The role of ubiquitin-mediated degradation mechanisms in the pathogenesis diffuse large B cell (DLBCL) and follicular lymphoma (FL) is not completely understood. We show that conditional deletion E3 ubiquitin ligase Fbxo45 germinal center B-cells results B-cell lymphomagenesis homozygous (100%) heterozygous (48%) mice. Mechanistically, FBXO45 targets RHO guanine exchange factor ARHGEF2/GEF-H1 for degradation. Double genetic ablation Arhgef2 ameliorated formation. Transgenic knock-in...
Deubiquitinating enzymes (DUbs) play important roles in many ubiquitin-dependent pathways, yet how DUbs themselves are regulated is not well understood. Here, we provide insight into the mechanism by which ubiquitination directly enhances activity of ataxin-3, a DUb implicated protein quality control and disease polyglutamine neurodegenerative disorder, Spinocerebellar Ataxia Type 3. We identify Lys-117, resides near catalytic triad, as primary site wild type pathogenic ataxin-3. Further...
Article13 October 2017Open Access Source DataTransparent process RBPJ/CBF1 interacts with L3MBTL3/MBT1 to promote repression of Notch signaling via histone demethylase KDM1A/LSD1 Tao Xu Department Pathology, University Michigan Medical School, Ann Arbor, MI, USA Search for more papers by this author Sung-Soo Park Benedetto Daniele Giaimo Institute Biochemistry, Giessen, Germany Daniel Hall Molecular Genetics, Biochemistry and Microbiology, Cincinnati College Medicine, Cincinnati, OH,...
Abstract Dysregulated ROR-γt-mediated IL-17 transcription is central to the pathogenesis of several inflammatory disorders, yet molecular mechanisms that govern factor activity ROR-γt in regulation are not fully defined. Here we show SUMO-conjugating enzyme Ubc9 interacts with a conserved GKAE motif induce SUMOylation and suppress expression. Th17 cells expressing SUMOylation-defective highly colitogenic upon transfer Rag1 –/– mice. Mechanistically, facilitates binding HDAC2 promoter...
Identification of biomarkers and therapeutic targets is a critical goal precision medicine. N-glycoproteins are particularly attractive class proteins that constitute potential cancer for small molecules, antibodies, cellular therapies. Using mass spectrometry (MS), we generated compendium 1,091 (from 40 human primary lymphomas cell lines). Hierarchical clustering revealed distinct subtype signatures included several subtype-specific biomarkers. Orthogonal immunological studies in 671...
<p>Supplementary Table S4, Whole genome sequencing of FL, DLBCL and transformed reveal loss FBXO45 as well copy number gain encompassing ARHGEF2, the gene that encodes GEF H1 protein. showing frequency genomic ARHGEF2 in respectively.</p>
<p>Supplementary Table S5, FISH analysis to identify copy number variations (CNV) affecting genes of interest within the corresponding genomic loci.</p>
<p>Supplementary Table S3, Quantitative whole proteome analysis of pooled sorted GCB-cells from Fbxo45 homozygous knockout mice compared with identically isolated cells wild-type littermates.</p>
<p>Supplementary Table S1 shows FBXO45 interactions by immunoprecipitation–tandem mass spectrometry. Normalized Spectral Abundance Factor (NSAF) was calculated as previously published (63). Average NSAFs (n = 3) for the indicated proteins are shown, and data were obtained from at least three independent experiments.</p>
<p>Supplementary Table S2, Mass spectrometric (MS) identification of GEF-H1-derived peptides in FBXO45 immunoprecipitation. FLAG-tagged expressing B-cell lymphoma cell lines were subjected to immunoprecipitation (IP) with anti-FLAG resin. MS analysis co-purified endogenous proteins revealed the presence numerous peptides.</p>
<p>Supplementary Table S7, showing source data and statistics for non-high-throughput experiments such as flow cytometry, quantitative PCR, protein other molecular cellular assays.</p>
<p>Supplementary Table S6, Details of the FISH probes used to identify copy number variations (CNV) affecting FBXO45 and ARHGEF2 in clinical samples.</p>
<p>Supplementary Data file shows all the supplementary figures, figure legends and table legends.</p>
<div>Abstract<p>The role of ubiquitin-mediated degradation mechanisms in the pathogenesis diffuse large B-cell lymphoma (BCL) and follicular is not completely understood. We show that conditional deletion E3 ubiquitin ligase <i>Fbxo45</i> germinal center B cells results lymphomagenesis homozygous (100%) heterozygous (48%) mice. Mechanistically, FBXO45 targets RHO guanine exchange factor ARHGEF2/GEF-H1 for degradation. Double genetic ablation <i>Arhgef2</i>...
Deregulation of signaling pathways controlled by protein phosphorylation underlies the pathogenesis hematological malignancies; however, extent to which deregulated may be involved in B-cell non-Hodgkin lymphoma (B-NHL) is largely unknown. To identify events important B-NHLs, we performed mass spectrometry-based, label-free, semiquantitative phosphoproteomic profiling 11 cell lines derived from three B-NHL categories: Burkitt lymphoma, follicular and mantle-cell lymphoma. In all, 6579 unique...
Kir2.1, a strong inward rectifier potassium channel encoded by the
Trace element selenium (Se) is incorporated as the 21st amino acid, selenocysteine, into selenoproteins through tRNA[Ser]Sec. Selenoproteins act gatekeepers of redox homeostasis and modulate immune function to effect anti-inflammation resolution. However, mechanistic underpinnings involving metabolic reprogramming during inflammation resolution remain poorly understood. Bacterial endotoxin lipopolysaccharide (LPS) activation murine bone marrow-derived macrophages cultured in presence or...
Repeat associated non-AUG (RAN) translation of CGG repeats in the 5'UTR FMR1 produces toxic proteins that contribute to fragile X-associated tremor/ataxia syndrome (FXTAS) pathogenesis. The most abundant RAN product, FMRpolyG, initiates predominantly at an ACG upstream repeat. Accurate FMRpolyG measurements FXTAS patients are lacking. We used data-dependent acquisition and parallel reaction monitoring (PRM) mass spectrometry coupled with stable isotope labeled standard peptides identify...
// Aradhana Awasthi 1, * , Delphine C.M. Rolland 9, Janet Ayello 1 Carmella van de Ven Venkatesha Basrur 8 Kevin Conlon Damian Fermin Matthew J. Barth 6 Christian Klein 7 Kojo S.J. Elenitoba-Johnson 9 Megan S. Lim ** and Mitchell Cairo 2, 3, 4, 5, Department of Pediatrics, New York Medical College, Valhalla, NY, USA 2 Medicine, 3 Pathology, 4 Microbiology & Immunology, 5 Cell Biology Anatomy, Roswell Park Cancer Institute, Buffalo, Roche Pharmaceutical Research Early Development,...